著者

Shinichi Yamashita Juntaro Koyama Takuro Goto Shinji Fujii Shigeyuki Yamada Yoshihide Kawasaki Naoki Kawamorita Koji Mitsuzuka Yoichi Arai Akihiro Ito

出版者

Tohoku University Medical Press

雑誌

The Tohoku Journal of Experimental Medicine (ISSN:00408727)

巻号頁・発行日

vol.252, no.3, pp.219-224, 2020 (Released:2020-11-03)

参考文献数

27

被引用文献数

13

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Testicular cancer occurs in the testes of the male reproductive system and is the most common cancer in adolescent and young adult (AYA) men. However, recently, there have been more cases of testicular cancer in men older than 40 years. Therefore, trends of testicular cancer during the past 40 years were retrospectively examined, focusing on age and histology. Patients who were diagnosed with testicular cancer at our institution between 1980 and 2019 were enrolled in this study. The patients were divided into groups by the year of diagnosis (1980s, 1990s, 2000s, and 2010s), age at diagnosis (14, 15 to 39, and older than 40 years), and histological type (seminoma and non-seminoma). A total of 563 patients were diagnosed with testicular cancer over the 40-year period. The median age at diagnosis increased continuously, from 28 years to 31 years, 34 years, and 38 years in each period, respectively (p < 0.001). Moreover, most testicular cancer patients were of the AYA generation, whereas the ratio of patients older than 40 years increased significantly since 2000 (p < 0.001). The relative proportion of seminoma also increased more than 50% since 2000. In the seminoma group, median age increased from 31 years to 41 years during the 40-year period (p < 0.001). In conclusion, the age at diagnosis is rising for testicular cancer patients. Clinicians should recognize that testicular cancer affects not only the AYA generation, but there has been a shift to older than 40 years, especially in seminoma.

著者

Kengo Nakahara Kana Fujikawa Hideki Hiraoka Ikuko Miyazaki Masato Asanuma Akihiro Ito Nobumasa Takasugi Takashi Uehara

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.42, no.6, pp.1044-1047, 2019-06-01 (Released:2019-06-01)

参考文献数

28

被引用文献数

12

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Nitric oxide (NO) is a key signaling molecule that has various effects via S-nitrosylation, a reversible post-translational modification that affects the enzymatic activity, localization, and metabolism of target proteins. As chronic nitrosative stress correlates with neurodegeneration, the targets have received focused attention. Macrophage migration inhibitory factor (MIF) plays a pivotal role in the induction of gene expression to control inflammatory responses. MIF acts as a ligand for CD74 receptor and activates the Src-p38 mitogen-activated protein kinase (MAPK) cascade. MIF also elevates the expression of brain-derived neurotrophic factor (BDNF), which contributes to the viability of neurons. Here, we show that MIF is S-nitrosylated by a physiological NO donor. Interestingly, the induction of S-nitrosylation resulted in a loss of MIF activity following stimulation of the Src and p38 MAPK signaling pathways and the induction of BDNF expression. Our results shed light on the pathogenic mechanisms of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease.

著者

Akihiro Ito Lei Wang Ryotaro Notomi Shigeki Sasaki Yosuke Taniguchi

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.72, no.1, pp.16-20, 2024-01-01 (Released:2024-01-01)

参考文献数

24

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Triplex DNA formation has generated much interest as a genomic targeting tool that directly targets duplex DNA. However, fundamental limitations in the base pairs of target duplex DNA sequences that can form stable triplex DNA have limited the application. Recently, we have reported on the recognition of CG and 5mCG base pairs by artificial nucleic acid derivatives with a 2′-deoxynebularine skeleton. Therefore, we attempted to explore the basic skeleton that is important for the development of new artificial nucleic acids allowing for the recognition of TA base pairs. In this study, we focused on a benzimidazole skeleton and introduced a hydroxyl group to enable one-point hydrogen bonding. We have synthesized artificial nucleoside analogues with hydroxyl group on the benzimidazole and incorporated their amidite derivatives into triplex forming oligonucleotides (TFOs). The gel shift assay was performed to evaluate the triplex DNA formation ability of synthesized TFOs, and TFOs containing hydroxybenzimidazole were successfully recognized TA base pairs for all four different sequences. Moreover, compared to the results for the TFOs containing benzimidazole, which suggested hydrogen bonding formation at the hydroxyl group. Therefore, hydroxybenzimidazole would be an important artificial nucleic acid skeleton for TA base pair recognition.

著者

Hiroshi Kobe Akihiro Ito Yosuke Nakanishi Akira Kuriyama Hiromasa Tachibana Tadashi Ishida

出版者

The Japanese Society of Internal Medicine

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

vol.61, no.15, pp.2273-2279, 2022-08-01 (Released:2022-08-01)

参考文献数

16

被引用文献数

3

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Objective The coronavirus disease 2019 (COVID-19) pandemic continues to spread across the world, and the utility of many drugs for treatment has been suggested. However, few studies have examined the efficacy and safety of treatment with baricitinib, remdesivir, and dexamethasone. Methods A retrospective, cohort study of patients who were admitted to Kurashiki Central Hospital in Japan between April 6 and June 29, 2021, was conducted. Differences in patients' background characteristics, clinical outcomes, and safety were investigated in the groups with and without baricitinib treatment. The primary outcome was the bacterial infection rate, and the secondary outcome was the 28-day mortality rate. An inverse probability of treatment weighting (IPTW) analysis, including 12 covariates, was used as a propensity score analysis to reduce biases. Results In total, there were 96 patients, including 43 in the baricitinib-containing therapy (BCT) group and 53 in the non-baricitinib-containing therapy (non-BCT) group. In the BCT group, the ordinal scale on admission was 2.3% with 4, 51.1% with 5, 23.3% with 6, and 23.3% with 7. In the non-BCT group, the ordinal scale was 1.9% with 3, 18.9% with 4, 58.5% with 5, 13.2% with 6, and 7.5% with 7. After adjusting by the IPTW analysis, the BCT group did not have an increased bacterial infection rate [odds ratio (OR), 1.1; 95% confidence interval (CI), 0.36-3.38; p=0.87] or 28-day mortality rate (OR, 0.31; 95% CI, 0.07-1.3; p=0.11) compared with the non-BCT group. Conclusion BCT can be administered without increasing the infection risk compared with non-BCT.

著者

Hiroshi Kobe Akihiro Ito Yosuke Nakanishi Akira Kuriyama Hiromasa Tachibana Tadashi Ishida

出版者

The Japanese Society of Internal Medicine

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

pp.9534-22, (Released:2022-05-31)

参考文献数

16

被引用文献数

3

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Objective The coronavirus disease 2019 (COVID-19) pandemic continues to spread across the world, and the utility of many drugs for treatment has been suggested. However, few studies have examined the efficacy and safety of treatment with baricitinib, remdesivir, and dexamethasone. Methods A retrospective, cohort study of patients who were admitted to Kurashiki Central Hospital in Japan between April 6 and June 29, 2021, was conducted. Differences in patients' background characteristics, clinical outcomes, and safety were investigated in the groups with and without baricitinib treatment. The primary outcome was the bacterial infection rate, and the secondary outcome was the 28-day mortality rate. An inverse probability of treatment weighting (IPTW) analysis, including 12 covariates, was used as a propensity score analysis to reduce biases. Results In total, there were 96 patients, including 43 in the baricitinib-containing therapy (BCT) group and 53 in the non-baricitinib-containing therapy (non-BCT) group. In the BCT group, the ordinal scale on admission was 2.3% with 4, 51.1% with 5, 23.3% with 6, and 23.3% with 7. In the non-BCT group, the ordinal scale was 1.9% with 3, 18.9% with 4, 58.5% with 5, 13.2% with 6, and 7.5% with 7. After adjusting by the IPTW analysis, the BCT group did not have an increased bacterial infection rate (odds ratio [OR], 1.1; 95% confidence interval [CI], 0.36-3.38; p=0.87) or 28-day mortality rate (OR, 0.31; 95% CI, 0.07-1.3; p=0.11) compared with the non-BCT group. Conclusion BCT can be administered without increasing the infection risk compared with non-BCT.

著者

Hiroshi Kobe Akihiro Ito Hiroki Hayata Keisuke Nishimura Yasunori Ueda Tadashi Ishida

出版者

The Japanese Society of Internal Medicine

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

vol.60, no.1, pp.131-136, 2021-01-01 (Released:2021-01-01)

参考文献数

22

被引用文献数

2

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A 76-year-old woman with dermatomyositis was being treated with prednisolone, tacrolimus, and mycophenolate mofetil. There was a solitary lung nodule in the right middle lobe on chest computed tomography at a routine follow-up examination. A transbronchial lung biopsy was performed, and the histopathologic findings indicated diffuse large B-cell lymphoma. An immunodeficiency-associated lymphoproliferative disorder was suspected, and mycophenolate mofetil was stopped without adding any other therapy. Nine months later, the pulmonary nodule had disappeared on chest computed tomography.